Non-Hodgkin's lymphomas (NHLs) are the 5th most common malignancy in the United States, with an incidence that has increased significantly over the last decade. Preliminary data obtained from Adult Lymphoma clinic at DFCI, as well as from Hodgkin's lymphoma patients treated at the Harvard Joint Center for Radiation Therapy (JCRT), show that 6-9% of these patients have a first-degree relative who also has a lymphoproliferative disorder. The goals of this research proposal are to systematically identify and characterize the subset of lymphomas associated with apparent familial predisposition and to determine whether their genetic basis can be identified. The Specific Aims of this project are: (1) to identify families with at least two first-degree relatives with lymphoproliferative malignancy and establish a data and tissue bank including serum, peripheral blood lymphocytes, germline DMA, and tumor tissue;(2) to investigate whether familial lymphomas have characteristic sites of loss of heterozygosity and to attempt to identify candidate genes within those regions;(3) to investigate whether familial lymphomas have characteristic patterns of global gene expression;(4) to perform a linkage analysis to identify candidate genes in the germline that may predispose to lymphoma development. These novel experiments should illuminate the biological underpinnings of familial lymphoma, which should in turn lead to targeted therapies and possibly methods of screening or prevention. This project will enable the candidate to use her scientific training in molecular biology to develop an academic career in clinical / translational investigation in lymphoma, applying novel scientific discoveries to the clinic. The research will be conducted primarily at Dana-Farber Cancer Institute and Harvard Medical School, where extensive clinical, scientific and faculty resources are available to ensure the completion of the project.